A number of female reproductive conditions exist which not only have adverse effects on fertility, but may pose serious health concerns to female sufferers, such as cancer. Such conditions include gestational trophoblastic diseases, such as the phenomenon of recurrent hydatidiform moles (HM), an abnormal human pregnancy with no embryo and cystic degeneration of placental villi. Recurrent HM is a rare clinical entity in which molar tissues are diploids and have a biparental contribution to their genome. In a number of cases this condition has been observed to have a familial basis. Recurrent hydatidiform molar tissues are undistinguishable at both gross morphology and histopathology levels from the common non-recurrent moles, which are androgenetic in most of the cases (80% of the cases), but may also be biparental (in 20% of the cases). The common form of hydatidiform moles occur in 1 in every 1500 pregnancies in western countries, but at a higher incidence in the Far East, Africa and Central America where the incidence of this condition may reach 1 in 100 pregnancies. Epidemiological studies performed to correlate this higher incidence with various environmental factors failed to reach significant conclusions, but shows a higher risk of hydatidiform moles at the beginning and end of a woman's reproductive cycle. In addition, the relative risk of developing a second HM after a previous molar pregnancy is 20 to 40 times the incidence of moles in the general population indicating genetic susceptibility to moles.
In mammals, maternal effect genes, in addition to those coding for oocyte mRNAs and proteins that accumulate in the egg during oogenesis, extend to genes required in the maternal reproductive tract for normal preimplantation and implantation development. Applicant has previously mapped a genetic region responsible for recurrent HMs to a 15-cM interval on 19q13.4 in two unrelated families, MoLb1 and MoGe2 (Moglabey et al., 1999). Additional families from various ethnic groups were reported and most of them were found linked to 19q13.4, indicating a major locus in this region leading to recurrent HMs. The analysis of these families narrowed down the HM candidate region to a 1.1-Mb interval (Sensi et al. 2000; Hodges et al. 2003).
Therefore, there is a continued need to identify the gene associated with such disorders.
The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety.